Changing osteocalcin concentrations during pregnancy and lactation: implications for maternal mineral metabolism

We measured serum osteocalcin concentrations in 82 pregnant and 21 nonpregnant women. Osteocalcin values declined in the second trimester, but returned to nonpregnant levels late in the third trimester. The mean serum osteocalcin concentration in 36 women during pregnancy (mean gestation, 26 weeks) of 2.8 ng/mL was significantly lower than that in nonpregnant women (6.4 ng/mL; P less than 0.001) or term pregnant women at delivery (6.1 ng/mL; n = 46). Serum immunoreactive PTH (iPTH) levels were significantly higher during pregnancy than in nonpregnant women [97 +/- 5 vs. 56 +/- 4 ng/L (mean +/- SE); P less than 0.001]. No significant correlations were found between maternal osteocalcin concentrations and serum phosphorus, alkaline phosphatase, or iPTH, but significant negative correlations were found between osteocalcin and total calcium or total protein. Osteocalcin concentrations in midtrimester amniotic fluid were very low (mean, 0.3 +/- 0.1 ng/mL; n = 11). In 29 lactating mothers, the mean serum osteocalcin level was 9.5 +/- 1.5 ng/mL, significantly higher than in any of the other groups (P less than 0.05), but their serum calcium and iPTH levels were normal. There was no correlation between serum osteocalcin and calcium or iPTH concentrations in lactating women. These changes are compatible with a sequence in which bone turnover is reduced during early pregnancy, rebounds in the third trimester, and increases in postpartum lactating women.     

Effect of chronic naltrexone and methadone administration on brain immunoreactive beta-endorphin in the rat

The effects of chronic treatment with methadone, a long-acting opiate agonist, and naltrexone, a long-acting opiate antagonist on brain immunoreactive beta-endorphin (IR-beta-EP) concentrations were studied in the rat. Male rats were treated for 30 days with either methadone, 2.5 mg/kg/day; naltrexone 2 mg/kg/day, or saline. In a repeat experiment, rats were treated for 36 days with either methadone 2.5 mg/kg/day; naltrexone 4 mg/kg/day, or saline. Brain regions were homogenized in 0.2 N HCl and assayed for IR-beta-EP by RIA. No change in the IR-beta-EP content of the hypothalamus, thalamus, midbrain, or amygdala was measured in either experiment after methadone treatment. Naltrexone, however, significantly lowered brain IR-beta-EP in both experiments. In the first study hypothalamic IR-beta-EP fell from 189 +/- 17 (SEM) to 132 +/- 7.0 ng/g wet weight of tissue after naltrexone treatment (p less than 0.01). In the second experiment naltrexone lowered IR-beta-EP in the hypothalamus from 23.4 +/- 3.6 to 15.5 +/- 1.2 ng/mg protein (p less than 0.005). Similar decreases in the IR-beta-EP content of the thalamus (from 6.74 +/- 0.59 to 4.59 +/- 0.38 ng/mg protein) and amygdala (from 1.31 +/- 0.08 to 0.90 +/- 0.10) were also measured (p less than 0.01). We conclude that occupancy of opiate receptors by an opiate antagonist reduces brain levels of IR-beta-EP and suggests that chronic opiate receptor blockade may result in a compensatory increase in brain beta-EP release.     

Megakaryocytopoiesis and platelet production are stimulated during late pregnancy and early postpartum in the rat.

Platelet count during uncomplicated pregnancy shows considerable patient variation. To gain a better understanding of thrombocytopoiesis during pregnancy, megakaryocytes and platelets were examined during gestation and the early postpartum period, using as a model the rat. Platelet counts and megakaryocyte concentrations and DNA content distributions of timed-pregnant rats were examined at intervals from day 10 of gestation through parturition on day 22 and days 1 through 7 postpartum. Platelet survival was studied in late gestation and the early postpartum. Platelet volume was measured on gestation day 21. Platelet counts were moderately increased on gestation days 17 and 19 through 22, and on days 2 to 3 postpartum. However, the actual rate of platelet production was much higher than the platelet count suggests because the blood volume increased in late gestation to 1.5 times the nonpregnant level. Mean platelet volume and platelet volume distribution width of day 21 gestation rats were not significantly altered. Platelet survival in pregnant rats was not significantly different from that in nonpregnant females. In contrast, megakaryocyte concentration was significantly increased on gestation days 12, 17, and 19 through 21, and 2 to 3 days postpartum. In addition, in late gestation, megakaryocyte DNA content distributions displayed a marked increase in the proportion of high ploidy cells, which peaked 1 day before parturition. At that time, the proportions of 32N (43%) and 64N cells (3%) were, respectively, three and four times nonpregnant values. In contrast to megakaryocyte concentration, megakaryocyte DNA content distributions had returned to the nonpregnant pattern by day 1 postpartum. The changes in megakaryocyte DNA content distribution were accompanied by changes in megakaryocyte size. These data indicate that thrombopoiesis is substantially increased during late pregnancy, and that this increase is accomplished through an increase in megakaryocyte DNA content and size, as well as megakaryocyte number. The more rapid return of megakaryocyte DNA content than of megakaryocyte concentration to nonpregnant levels postpartum suggests that pregnancy-associated hormonal changes which produce an increase in megakaryocyte DNA content and size differ from those which cause an increase in megakaryocyte number.     

Hypothalamic opiatergic tone during pregnancy, parturition and lactation in the rat.

The concentrations of beta-endorphin have been shown to change in the rat brain during pregnancy and lactation. This study has been performed in order to analyze whether also brain opioid receptors might undergo significant modifications during these two physiological situations. The maximal binding capacity (Bmax) and the constant of affinity (Ka) of the mu-subpopulation of opioid receptors have been evaluated in the hypothalami of female rats at different stages of pregnancy (7, 15 and 22 days), on the day of parturition (12-18 h after delivery) and 6-8 days postpartum (both in lactating and in nonlactating animals). Female rats killed on the day of estrus served as controls. The receptor binding assay has been performed utilizing [3H]-dihydromorphine [( 3H]-DHM) as the ligand for the mu-opioid receptors. Hypothalamic concentrations of beta-endorphin as well as serum levels of luteinizing hormone (LH), follicle-stimulating hormone (FSH) and prolactin have also been evaluated by radioimmunoassay. The results showed that the concentration of hypothalamic mu-opioid receptors increased during pregnancy, being significantly higher than in the controls at days 15 and 22 of gestation. After delivery, the concentration of these receptors returned towards control values, regardless on whether the animals were lactating or not. The Ka values of [3H]-DHM for the mu-receptors did not change significantly in the different groups of experimental animals. Hypothalamic beta-endorphin content showed a modest though not significant increase at the end of gestation (day 22) and returned to control values 12-18 h after delivery.(ABSTRACT TRUNCATED AT 250 WORDS)     

Serum osteoprotegerin as a determinant of bone metabolism in a longitudinal study of human pregnancy and lactation

Osteoprotegerin (OPG) is a soluble decoy receptor that inhibits bone resorption by binding to receptor activator of nuclear factor kappa B ligand. Murine studies suggest that OPG is elevated in pregnancy, but its role in human pregnancy is unknown. We evaluated the relationship among OPG, bone turnover, and bone density in a longitudinal study of planned human pregnancy and lactation (n = 17; age, 20-36 yr). Samples were collected before conception; at 16, 26, and 36 wk gestation; and at 2 and 12 wk postpartum. Indexes of bone resorption included serum beta C-terminal and urinary N-terminal (uNTX) telopeptides of type I collagen. OPG increased by 110 +/- 16% (mean +/- SEM) at 36 wk (P < 0.001), followed by a rapid postpartum decline in both lactating and nonlactating women. Bone resorption was elevated at 36 wk (serum beta C-terminal telopeptides by 76 +/- 17%; urinary N-terminal telopeptides by 219 +/- 41%; P < 0.001). The tissue source of OPG in pregnancy is unknown. Human breast milk contains large amounts of OPG (162 +/- 58 ng/ml in milk vs. 0.42 +/- 0.03 ng/ml in nonpregnant serum). However, the rapid postpartum decline in serum OPG and the low serum OPG in neonates suggest a placental source. There was no correlation between change in OPG and bone turnover or bone mineral density (P > 0.05), and the physiological importance of elevated OPG in human pregnancy remains uncertain.     

Osteocalcin as an index of osteoblast function during and after ovine pregnancy

Fetal and neonatal calcium requirements impose heavy demands on maternal bone and mineral homeostasis. The functional response of maternal osteoblasts to this stress is poorly understood. Therefore, plasma osteocalcin (OC) levels were measured by homologous RIA in age-matched nonpregnant, pregnant, and postpartum ewes to evaluate osteoblast function. In pregnant ewes from day 35 of gestation to term, the plasma OC level was suppressed to 8.2 +/- 0.5 micrograms/liter (mean +/- SEM; n = 36) compared with age-matched nonpregnant ewes (18.3 +/- 1.1 micrograms/liter; n = 39; P less than 0.0005). Plasma OC rose to the nonpregnant value by day 20 postpartum and was elevated above this level for the following 40 days (e.g. 44.0 +/- 5.0 micrograms/liter at 48-53 days; P less than 0.0005). The timing of changes in plasma OC levels and weaning did not correlate. The validity of plasma OC measurement as a marker of osteoblast function was assessed by determining the OC plasma production and clearance rates using an [125I]ovine OC infusion method. The OC plasma production rates in matched controls (n = 6), pregnant (n = 9), and 48-53-day postpartum sheep (n = 7) were 1.5 +/- 0.2, 0.5 +/- 0.04 (P less than 0.001 vs. control), and 3.6 +/- 0.6 mg/day (P less than 0.005 vs. pregnant sheep), respectively. In one ewe studied longitudinally, the OC plasma production rate increased by 15 days after parturition and achieved a 10-fold elevation at 49 days postpartum. The OC plasma clearance rate (3.3 +/- 0.3 liters/h) was the same in control, pregnant, and postpartum ewes. It is concluded that 1) changes in plasma OC levels during and after ovine pregnancy reflected changes in OC production, 2) plasma OC measurements are likely to be a useful index of osteoblast function in pregnancy, and 3) osteoblast function appears to be depressed during ovine pregnancy and enhanced markedly in the interval 20-60 days postpartum. The relationship between osteoblast function, as indicated by OC production, and bone formation remains to be clarified.     

Respiratory effects of pregnancy and progesterone in Jersey cows

Unanesthetized Jersey cows were studied during both pregnant (5-9 months) nonlactating states, and nonpregnant lactating states; and also following treatment with progesterone (Pr). The pH, PCO2 and PO2 of aortic blood, VE and f were measured and the mixed expired gas was analyzed. The following significant changes from the nonpregnant state occurred during pregnancy: PaCO2 = -3.2 mm Hg, pHa = +0.02 unit, VT = -0.44 L, f = +7 breaths/min, and VE/VCO2 = +9.7. Concomitant with the respiratory studies, serum Pr levels were determined by radioimmunoassay (RIA) in 11 nonpregnant and 5 pregnant cows, and in 6 nonpregnant, lactating cows prior to and on days 3, 5 and 10 of treatment with Pr (500 mg, i.m., twice daily). Minute ventilation (VE, L X min-1 X kg-1, BTPS) was positively correlated (r = +0.59) and PaCO2 was negatively correlated (r = -0.64) with endogenous serum Pr levels of non-pregnant and pregnant cows. However, exogenous Pr did not significantly alter these parameters or pHa, despite mean serum levels nearly twice (23.6 +/- 10.2 ng/ml) those observed in pregnant cows (12.7 +/- 3.7 ng/ml). The increased ventilation during pregnancy in Jersey cows, shown in this study, does not appear to be related to Pr as exogenous Pr failed to induce hyperventilation. The correlation of increased ventilation with endogenous Pr levels therefore suggests that the mode of in vivo Pr release, or different compound, simultaneously released, could be the stimulus.     

Regulation of serum insulin-like growth factor-I (IGF-I) and IGF binding proteins during rat pregnancy.

Serum concentrations of insulin-like growth factor-I (IGF-I) in rats are reduced dramatically in the latter half of pregnancy, decreasing from 1758 +/- 356 ng/ml at 12 days of pregnancy (mean +/- SD) to 761 +/- 192 ng/ml at 15 days. After parturition, IGF-I increases to nonpregnant values in 4 days. Using ligand blotting, we have demonstrated that most of the serum IGF binding proteins (IGFBPs) are concurrently reduced during pregnancy. IGFBP-3, the predominant IGFBP in nonpregnant serum, is reduced to 1.3% of nonpregnant values by 21 days of pregnancy and begins to rise within 1 h postpartum (PP). The sera of 21-day pregnant (but not nonpregnant) rats degrade IGFBP-3 in vitro, and this degradation is prevented by the protease inhibitor antipain. Decreased serum IGF-I concentrations during pregnancy, therefore, may result from reduced IGFBP-3 concentrations causing increased IGF-I clearance. In addition, steady state IGF-I mRNA and peptide levels in liver are decreased in 21-day pregnant rats (37% and 42% of 4 day PP levels, respectively), suggesting that decreased synthesis of IGF-I may also lead to lower serum IGF-I concentrations. After bolus injection, [125I]IGF-I is cleared from the serum of pregnant rats nearly 5 times faster than that of 4 day PP rats (1.21 vs. 0.25 ml/min/kg, respectively). Urinary clearance is relatively insignificant (less than 4%), and [125I]IGF-I does not cross the placenta. The intermediate distribution phase of IGF-I is slower in pregnant rats than in PP rats (t1/2 alpha, 17.1 vs. 5.4 min), whereas the terminal elimination of IGF-I is twice as fast (t1/2 beta, 228.1 vs. 106.4 min). The prolonged IGF-I distribution phase in the pregnant rats may result from decreased concentrations of 34,000 and 30,000 mol wt IGFBPs, which may transport IGF-I to tissues. The faster serum elimination half-life may result from diminished IGFBP-3, leading to greater IGF-I availability to tissues in pregnancy.     

Plasma progesterone through pregnancy and the estrous cycle in the eastern quoll, Dasyurus viverrinus

Plasma progesterone concentrations were measured every 2 or 3 days in eastern quoll, Dasyurus viverrinus, during pregnancy (20.5 +/- 0.8 days, n = 6, mean +/- SEM) and the estrous cycle (37.5 +/- 0.7 days, n = 20, mean +/- SEM). The pattern was not apparently different between the two reproductive states. There was a significant proestrus rise in progesterone (from 0.5 to 4 ng/ml) from 5 days before until 1 day after mating. For the next 4 to 6 days, levels were low, but after Day 9 or 10 increased to maximum concentrations of 4.5 to 15 ng/ml which were maintained until about Day 17 to 19. In all females, progesterone was basal (less than 1.0 ng/ml) by Day 20 to 21 and thereafter remained low in lactating females, but nonpregnant females showed a proestrous rise about 5 to 7 days before the next mating. The period of elevated concentrations of progesterone coincided with prominent corpora lutea (CL) on the ovaries. There was no evidence of CL of a previous cycle persisting into the next cycle. The results indicate that pregnancy occupies the luteal phase of the cycle and does not appear to influence the secretory life span of the CL.     

Plasma and amniotic fluid immunoreactive neuropeptide-Y level changes during pregnancy, labor, and at parturition

This study was designed to determine the presence of and possible changes in plasma and amniotic fluid immunoreactive neuropeptide-Y (irNPY) levels in pregnant women during gestation and at parturition. We studied 127 healthy pregnant and 12 nonpregnant women. The peptide was extracted from plasma or amniotic fluid with a propanolformic acid mixture and measured by RIA. The mean plasma irNPY concentration in 15 pregnant women during the first trimester of gestation was 129 +/- 12 (+/- SE) pmol/L, compared to 40 +/- 8 pmol/L in nonpregnant women (p less than 0.01). The mean values were 144 +/- 13 and 156 +/- 24 pmol/L, respectively, in 15 pregnant women during the second trimester and 33 women during the third trimester. These values did not differ from that during the first trimester. Amniotic fluid irNPY levels were similar to those in plasma and did not vary among the 3 groups of women studied during the various trimesters of gestation. During labor, plasma irNPY levels progressively increased, reaching the highest levels at the most advanced stages of cervical dilatation (greater than 8 cm, 351 +/- 38 pmol/L) and at the time of vaginal delivery (416 +/- 73 pmol/L). Plasma irNPY levels then decreased significantly 2 h after vaginal delivery. The amniotic fluid irNPY levels in women during the early or late stages of labor were similar. Moreover, plasma and amniotic fluid irNPY levels at the time of elective cesarean section also were similar. These results indicate that pregnant women have high plasma and amniotic fluid irNPY levels and that the stress of labor results in a further increase in plasma levels, suggesting a possible role of NPY in human pregnancy and parturition.     

Factors related to gastric hypersecretion during pregnancy and lactation in rats

We attempted to elucidate the factor involved in gastric hypersecretion of rats during pregnancy and lactation. Acid secretion in pylorus-ligated and vagally denervated fistula rats stimulated with histamine, tetragastrin, and methacholine increased from midterm pregnancy and persisted during lactation. Pepsin secretion remained unaltered during pregnancy but increased during lactation. Vagal denervation itself abolished this hypersecretion. In late pregnancy, a delayed appearance of maximal acid response to histamine was apparent, as compared to nonpregnant rats, and was abolished by aminoguanidine treatment. There was a delay in the maximal response to tetragastrin but not to methacholine. Serum histamine concentrations were 3–4 times higher in late pregnancy, as compared to nonpregnant, lactating and nonlactating rats. Gastric DNA and protein concentrations were significantly increased in lactating rats with concomitant elevation of food intake and serum gastrin levels. Those changes disappeared in nonlactating rats, and gastric secretion was much the same in the nonpregnant rats. These results indicate that acid hypersecretion during pregnancy was exclusively associated with vagal innervation plus high serum histamine levels, while acid and pepsin hypersecretion in lactating rats were associated with vagal innervation plus hyperplastic gastric mucosa and high serum gastrin levels.     

Regional concentrations of insulin in the rat brain

Recent evidence that insulin receptors are concentrated in the hypothalamus and olfactory bulb suggests that insulin may have an important regulatory function in these regions. This hypothesis would be supported by finding that insulin itself is concentrated in the hypothalamus and olfactory bulb. Therefore, we extracted the hypothalamus and olfactory bulb, as well as the amygdala, hippocampus, cerebral cortex, hindbrain, midbrain, and whole brains, of fasted male Wistar rats and measured immunoreactive insulin (IRI). Recovery of insulin added to extraction volumes of 500-1000 microliters was 90-100%, whereas recovery of insulin from tissue extracts was 63%. Mean IRI concentrations were relatively uniform throughout the brain (0.19 ng/g wet wt; uncorrected for recovery) and were significantly lower than plasma levels (1.03 ng/ml). Nevertheless, IRI concentrations were significantly higher in hypothalamus (0.39 +/- 0.02 ng/g; P less than 0.01) and olfactory bulb (0.37 +/- 0.02 ng/g; P less than 0.05) compared to those in other brain regions sampled.     

Plasma corticotropin-releasing hormone concentrations during pregnancy and parturition

Plasma CRH was measured in maternal plasma throughout the third trimester of pregnancy, during labor, and postpartum. CRH levels were also measured in arterial and venous umbilical cord plasma samples. In normal pregnant women, plasma CRH increased from 50 +/- 15 (+/- SEM) pg/mL at 28 weeks gestation (n = 41) to 1462 +/- 182 pg/mL at 40 weeks (n = 55) and 1680 +/- 101 pg/mL (n = 65) in labor. Women with pregnancy-induced hypertension (n = 49) had plasma CRH levels significantly elevated above this normal range. Similarly, women who subsequently went into premature labor had raised levels several weeks before the onset of labor. After delivery, plasma CRH returned to normal within 15 h. Total plasma cortisol levels varied little throughout the third trimester, but increased during labor and remained elevated 2-3 days postpartum. There was, therefore, no correlation between plasma cortisol and CRH, implying that this placental CRH is not primarily involved in the control of the maternal hypothalamo-pituitary adrenal axis during pregnancy. The concentrations of CRH in umbilical cord plasma samples were considerably lower than those in the maternal circulation and were close to those in normal nonpregnant adults.     

Brain histamine levels in the hamster during the estrous cycle and on selected days of pregnancy

Brain histamine levels were determined in golden hamster hypothalamus and 'brain minus hypothalamus' on each of the 4 days of the estrous cycle and on selected days of pregnancy. The highest histamine content of the hypothalamus was observed on day 3 of the estrous cycle. The highest histamine content of the hypothalamus was observed on day 3 of the estrous cycle, which is the day prior to recurrence of heat on day 4. Day 4 terminates in ovulation. The histamine level in the remainder of the brain peaked on day 2. During gestation the histamine content of the 'brain minus hypothalamus' was greatest on day 5, while the maximum content of histamine in the hypothalamus was not reached until day 8. After the 8th day of pregnancy, there was an overall decline in brain histamine that continued until parturition. The hypothalamic histamine level in nonpregnant females was not different from that of males. However, in the remainder of the brain, histamine levels in females on days 1 and 2 of the estrous cycle were higher than in males.     

Precise timing for peak relaxin and decreased progesterone secretion after hysterectomy in the pig

Relaxin and progesterone secretion by aging corpora lutea (days 90-120) was examined in pregnant and lactating gilts compared with that in hysterectomized animals. The length of pregnancy is about 115 days in pigs. Unmated gilts were hysterectomized on day 6 (estrus = day 0). From days 90-101, relaxin concentrations in peripheral plasma remained consistently low in pregnant gilts (range, 0.7-1.5 ng/ml) and less (P less than 0.05) than those in hysterectomized animals (range, 0.9-3.5 ng/ml). Relaxin increased abruptly (P less than 0.01) to a peak of 66 ng/ml in pregnant gilts and 37 ng/ml in hysterectomized animals. Relaxin peaked in pregnant animals at 113 +/- 0.7 days (+/- SE) and in hysterectomized gilts at 113 +/- 0.7 days; gestation length averaged 114 +/- 0.8 days. In pregnant gilts, relaxin decreased from a peak of 66 to 11 ng/ml within 1 day and remained low (less than 1.0 ng/ml) in these lactating dams until day 120. In hysterectomized gilts, peak relaxin also decreased abruptly from 37 to 4.2 ng/ml, but remained consistently greater (P less than 0.05) than that in lactating dams. Although there were abrupt shifts in relaxin concentrations within 20 min, there was no evidence for consistent episodic relaxin release between days 112-116. Plasma progesterone concentrations were consistently greater (P less than 0.05) in hysterectomized than in pregnant gilts from days 102-110. Progesterone decreased abruptly in prepartum gilts (days 111-114) from 16 to 1.2 ng/ml and remained low during lactation (0.5 ng/ml). In hysterectomized animals, it decreased abruptly on days 110-113, ranging from 20-12 ng/ml, and remained at this lower level until day 120. These results clearly indicate that a precisely timed peak release of relaxin and coincident decrease in progesterone secretion occur in unmated hysterectomized gilts at the same time as those found a few hours preceding parturition during normal pregnancy. These abrupt shifts in relaxin and progesterone secretion on days 112-113 in both hysterectomized and pregnant gilts may be regulated autonomously from within the ovary or from the central nervous system and pituitary gland.     

Immunoreactive beta-endorphin concentrations in brain and plasma during pregnancy in rats: possible modulation by progesterone and estradiol

Changes in opioid concentrations in brain and plasma as well as opioid activity have been reported to occur as a function of pregnancy and lactation in rats. The present study examines the status and steroidal regulation of the endogenous opioid, beta-endorphin, in the behaviorally and neuroendocrinologically important preoptic area (POA) and hypothalamus, and in the plasma of pregnant and nonpregnant rats. In the first study, concentrations of beta-endorphin-like immunoreactivity (beta-EP-LI-Ir) in POA and hypothalamic tissues as well as in plasma were measured throughout gestation in rats. beta-EP-LI-Ir concentrations in the POA were significantly higher in rats from day 6 to 18 of gestation than in nonpregnant, diestrous females. beta-EP-LI-Ir concentrations in the POA declined significantly between day 18 and 22 of gestation. Changes in hypothalamic beta-EP-LI-Ir concentrations were not detected either as a function of pregnancy or during pregnancy, while plasma beta-EP-LI-Ir concentrations declined gradually from day 6 to 18 of pregnancy and then increased significantly prepartum (day 22 of gestation). In the second study, the effects of 2 weeks of exposure to pregnancy levels of progesterone and estradiol on brain and plasma beta-EP-LI-Ir were measured. Exposure to the combination of progesterone and estradiol (administered subcutaneously via Silastic capsule implants) resulted in a significant increase in beta-EP-LI-Ir concentrations in the POA, but did not affect beta-EP-LI-Ir concentrations in either the hypothalamus or plasma.(ABSTRACT TRUNCATED AT 250 WORDS)     

Serum progesterone, estradiol-17 beta, and glucocorticoids in the collared peccary during gestation and lactation as influenced by dietary protein and energy

Sixteen pregnant collared peccaries were assigned to four experimental diets representing two levels of crude protein and two levels of digestible energy. Serum levels of progesterone, estradiol-17 beta (E2), and glucocorticoids were measured by radioimmunoassay. There was no significant dietary effect (P greater than 0.05) associated with any hormone during gestation. Progesterone did not differ between days 11 and 140 of gestation (X +/- SE = 36.48 +/- 1.11 ng/ml, N = 72), began to decline during the last week prepartum, and continued to decline within 24 hr of birth. Glucocorticoid concentrations remained level throughout gestation (X +/- SE = 6.57 +/- 0.45 microgram/dl, N = 74). E2 levels were low during the first 90 days of gestation, rose significantly (P less than 0.001) from 10.11 +/- 1.73 pg/ml (X +/- SE, N = 8) at Days 81-90 gestation to 49.07 +/- 12.87 pg/ml (N = 3) at 2-4 days prepartum (Days 141-147 of gestation), and declined rapidly to baseline levels within 24 hr of farrowing. Litter size had no effect on progesterone or E2 concentrations. There was no significant dietary effect on litter size or gestation length. During lactation, glucocorticoids and E2 remained stable and did not differ by diet, while progesterone concentrations appeared to be affected by diet. Individuals on the high energy-high protein diet returned to normal ovarian function before animals on the other three diets. Results indicated that the pregnant collared peccary can maintain a reproductive steroid environment that allows for fetal development in the face of moderate caloric or protein restriction and that the lactating peccary can undergo a postpartum ovulation in the presence of good nutrition.     

Estradiol regulation of proopiomelanocortin gene expression and peptide content in the hypothalamus.

Previous studies have shown that the hypothalamic concentrations of beta-endorphin (beta-EP) and other proopiomelanocortin (POMC)-derived peptides change in the female rat following castration and gonadal steroid replacement. In this study we have measured POMC mRNA by solution hybridization assay in the medial basal hypothalamus (MBH) of ovariectomized rats treated with a regimen of estradiol (E2) that we have previously shown alters brain beta-EP peptide content. In addition the effect of progesterone (P) was also studied. In the first experiment the concentration of beta-EP and alpha-melanocyte-stimulating hormone (alpha-MSH) in the MBH of castrated rats decreased significantly after 3 weeks of E2 treatment compared to castrated unreplaced rats: beta-EP decreased from 6.00 +/- 0.46 to 4.32 +/- 0.38 ng/mg protein and alpha-MSH decreased from 3.00 +/- 0.23 to 2.35 +/- 0.15 ng/mg protein (p less than 0.05). A similar decrease in peptide content was noted in the anterior hypothalamus/preoptic area. A parallel reduction in the concentration of POMC mRNA was measured in the MBH of the E2-replaced animals: 1.17 +/- 0.14 vs. 0.72 +/- 0.08 pg/microgram RNA (p less than 0.02). In a second study castrated rats were studied after 2 weeks of E2 or E2 plus P treatment. After 2 weeks, POMC peptide levels did not change significantly in the MBH of either the E2- or E2 plus P-treated rats. POMC mRNA, however, was significantly reduced from 1.10 +/- 0.10 pg/micrograms RNA in the unreplaced rats to 0.58 +/- 0.05 and 0.61 +/- 0.06 pg/microgram RNA after E2 or E2 plus P, respectively (p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)     

Hormonal regulation of medial preoptic mu-opiate receptor density before and after parturition.

Endogenous opioid peptides acting in the medial preoptic area (MPOA) appear to be involved in the regulation of maternal behavior in lactating rats. Moreover, it is known that the density of mu-opiate receptors in the MPOA is elevated during pregnancy, but decreases during lactation. In the first experiment of this study, mu-receptor density in the preoptic area was examined across the periparturitional period on gestation days 18, 20 and 22, at 1 h postpartum and on postpartum days 1 and 12. The effect of pregnancy during lactation on mu-receptor density was also assessed. In addition, plasma hormone concentration of estradiol (E2), progesterone (P), and prolactin (PRL) were determined. While plasma P levels decreased and PRL levels increased prior to parturition, MPOA mu-receptor density remained elevated until 24 h after parturition before declining to reach a level similar to that of ovariectomized control animals. Receptor density was significantly correlated with PRL levels only in gestation day 22 animals, when PRL levels were highest. MPOA mu-receptor density was low at postpartum day 12 whether or not the animal was pregnant. No effects were observed in the adjacent lateral preoptic area in any group. In the second experiment, the effect of hormonal manipulation on preoptic opiate receptor density was examined at various times after removal of Silastic capsules containing P following sustained E2/P exposure. While P levels decreased abruptly following capsule removal, MPOA receptor density declined more gradually. The results are consistent with the hypothesis that a reduction of mu-receptor density occurs in the MPOA following parturition by receptor turnover in the absence of sufficient hormonal stimulation.(ABSTRACT TRUNCATED AT 250 WORDS)     

Changes in the concentration of 17 alpha,20 alpha-dihydroxypregn-4-en-3-one during pregnancy, labor, and delivery and the effect of dexamethasone treatment during the third trimester of pregnancy

To study whether an alteration of placental steroid metabolism occurs during human pregnancy similar to that in the ewe, we measured the concentration of 17 alpha,20 alpha-dihydroxypregn-4-en-3-one (17,20 alpha-OHP) in peripheral plasma. As the pregnant ewe nears term, the utero-ovarian venous concentrations of 17,20 alpha-OHP increase, suggesting induction of placental 17 alpha-hydroxylase. The mean plasma concentration of 17,20 alpha-OHP measured by RIA in normal menstruating women was 1.1 +/- 0.12 (+/- SE) ng/ml. Similar values were found in plasma from ovariectomized women. In the first and second trimesters of pregnancy, the plasma values of 17,20 alpha-OHP were not significantly different from those in the nonpregnant women, while in the third trimester, the mean plasma concentration was significantly increased (mean +/- SE, 2.6 +/- 0.3 ng/ml). The plasma concentration of 17,20 alpha-OHP was studied in 15 women in late pregnancy, during labor, at delivery, and postpartum. The concentration increased during labor as delivery approached and reached a maximum at the time of delivery, ranging from 4.1-11.2 ng/ml, followed by a significant decrease within 1-4 h postpartum. The mean (+/- SE) 17,20 alpha-OHP concentrations in the venous and arterial cord blood were 8.7 +/- 1.6 and 5.8 +/- 2.0 ng/ml, respectively. To study the effect of increased circulating level of corticosteroids on the serum concentration of progestins, 74 women with premature labor with or without premature rupture of membranes were treated with either placebo or 4 im injections of dexamethasone phosphate (5 mg each) at 12-h intervals. Blood samples were drawn at 0, 14, 26, and 46 h, approximately 2 h after each dexamethasone dose. Plasma progesterone, 17 alpha-hydroxyprogesterone (17-OHP), and 17,20 alpha-OHP values at zero time were 140 +/- 15.8 (+/- SE; n = 21), 7.8 +/- 1.5 ng/ml (n = 16), and 2.3 +/- 0.3 ng/ml (n = 20), respectively. In patients treated with dexamethasone, the plasma progesterone values tended to increase at 14, 20, and 46 h, but 17-OHP and 17,20 alpha-OHP values decreased significantly compared to levels in placebo-treated patients. In conclusion, the concentration of plasma 17,20 alpha-OHP increased during the third trimester of pregnancy, and the increment continued through labor and delivery. During antenatal dexamethasone administration, progesterone in the maternal circulation tended to increase, while 17-OHP and 17,20 alpha-OHP decreased significantly. In the human, in contrast to the ewe, dexamethasone treatment in the third trimester does not appear to stimulate placental 17 alpha-hydroxylase activity.